Magnetic resonance diagnostic apparatus

ABSTRACT

In an improved INEPT pulse sequence, an excitation pulse, a refocus pulse and an excitation pulse are sequentially applied for  1  H spins. A refocus pulse and an excitation pulse are sequentially applied for  13  C spins that are spin-spin coupled with the  1  H spins. A magnetic resonance signal is acquired from  1  H spins or  13  C spins. The second refocus pulse for  1  H is applied as a slice selective pulse at a time different from the time the first refocus pulse for  13  C is applied. This allows localization to be achieved without adversely affecting the flip angle of the first refocus pulse for  13  C.

This application is a Division of application Ser. No. 08/909,948 Filedon Aug. 12, 1997, now U.S. Pat. No.5,894,221, which is a Division ofapplication Ser. No. 08/617,654, Filed Mar. 15, 1996, now U.S. Pat. No.5,677,628.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to a magnetic resonance diagnostic apparatus whichacquires information about relatively insensitive nuclear species, suchas ¹³ C, with high sensitivity.

2. Description of the Related Art

Attention has been paid to the observation of spectra of nuclear speciessuch as ¹³ C in that information about biochemistry such as metabolismor energy metabolism can be obtained. Assuming the sensitivity of ¹ H tobe unity, the sensitivity of ¹³ C is as low as about 1/4. Thus, therearises a problem in that the signal-to-noise ratio becomes very low.

Methods of improving the signal-to-noise ratio by employing largepolarization of ¹ H have been developed recently, which are roughlyclassified into two categories: ¹³ C observation (polarization transfermethod) and ¹ H observation. ¹³ C observation methods include INEPT(Insensitive Nuclei Enhanced by Polarization Transfer) methods and DEPT(Distortionless Enhancement by Polarization Transfer) methods. ¹ Hobservation methods include HSQC (Heteronuclear SingleQuantum-Coherence) methods and HMQC (Heteronuclear MultipleQuantum-Coherence) methods.

Hereinafter each of the above methods will be described. In thefollowing description, ¹ H combined with ¹³ C is represented by "¹ H{¹³C}". A radio-frequency magnetic field pulse (RF pulse) that selectivelyrotate ¹ H or ¹³ C spins through α° with respect to the β axis (β=x, y,pr z) is represented by a "α° β(¹ H or ¹³ C) pulse". The spin--spincoupling constant of ¹ H and ¹³ C is represented by J.

FIG. 1 shows an INEPT pulse sequence, and FIG. 2 shows the state of ¹ Hspin at time ta after a lapse of time 1/(4J) from the application of a180° (¹³ C) pulse. For ¹ H a 90° x(¹ H) pulse, a 180° y(¹ H) pulse and a90° y(¹ H) pulse are produced in sequence. For ¹³ C a 180° (¹³ C) pulseand a 90° (¹³ C) pulse are produced in sequence. The 180° y(¹³ C) pulseand the 180° (¹³ C) pulse are produced simultaneously. The 90° y(¹ H)pulse and the 90° (¹³ C) pulse are produced simultaneously. The timeinterval between the 90° x(¹ H) pulse and 180° (¹³ C) pulse is set to1/(4J). The time interval between the 180° (¹³ C) pulse and 90° y(¹ H)pulse is also set to 1/(4J). FIG. 3 shows a spectrum of data detectedfrom ¹³ C, which allows various metabolic functions to be diagnosed.

FIG. 4 shows an INEPT pulse sequence which has an additional decouplingpulse produced for ¹ H at data acquisition time. FIGS. 5 and 6 showINPET pulse sequences which have additional 180° pulses produced for ¹ Hand ¹³ C to rephase their spins. FIG. 7 shows a polarization transferpulse sequence which has no 180° pulse. Even with a 180° pulse removed,polarization transfer can be made, but its efficiency is low because the¹ H spins are not refocused.

FIG. 8 shows a DEPT pulse sequence, in which a 90° x(¹ H), a 180° x(¹ H)pulse and a θ° y(¹ H) pulse are produced sequentially for ¹ H, and a 90°(¹³ C) and a 180° (¹³ C) pulse are produced sequentially for ¹³ C. The180° x(¹ H) pulse and the 90° (¹³ C) pulse are produced simultaneously.The θ° y(¹ H) pulse and the 180° (¹³ C) pulse are producedsimultaneously. The time interval between the 90° x(¹ H) pulse and 90°(¹³ C) pulse is set to 1/(2J). The time interval between the 90° (¹³ C)pulse and θ° y(¹ H) pulse is also set to 1/(2J).

FIG. 9 shows an HSQC pulse sequence. The INEPT pulse sequence indicatedby block A allows polarization transfer to be made. Signals are thenobserved from ¹ H after a single-quantum coherence period t1 for ¹³ Cduring which time a chemical shift of ¹³ C is developed and areverse-INEPT pulse sequence indicated by block B. Since J coupling isrefocused by a 180° pulse at the center of the period t1, only the ¹³ Cchemical shift is developed during the t1 period. Two-dimensional dataS(t1, t2) is acquired by repeating the pulse sequence of FIG. 9 whilechanging the length of the interval t1. By subjecting the resultant datato two-dimensional Fourier transform, such a spectrum distribution σ(ω¹H, ω¹³ C) as shown in FIG. 10 is obtained.

FIG. 11 shows an HMQC pulse sequence. In HMQC, signals are observed from¹ H after a lapse of a multiple-quantum coherence period t1 during whichtime ¹³ C chemical shift is developed. Data S(t1, t2) is acquired byrepeating the pulse sequence of FIG. 11 while changing the length of theperiod t1. The resultant data is subjected to two-dimensional Fouriertransform to produce such a spectrum distribution as shown in FIG. 12.

With the ¹ H observation, it is essential to remove water signals.

With the HSQC pulse sequence of FIG. 9, water signals are removed by aCHESS (chemical shift selective) pulse.

An important problem with the HSQC and HMQC methods is to remove watersignals. However, the above-described methods cannot remove ¹ H in, forexample, glucose (CH) which has a chemical shift close to that of ¹ H inwater.

FIG. 13 shows an HSQC pulse sequence in which gradient magnetic fieldpulse Gsel for selecting only coherence of ¹ H{¹³ C} are added in orderto remove water signals.

FIGS. 14 and 16 show HMQC pulse sequences which are improved to removewater signals. FIG. 15A shows the state of magnetization of ¹ H at timeta after a lapse of 1/(4J) from the 180° (¹³ C) pulse in the INEPTsequence of FIGS. 14 and 16. In FIG. 14, the third proton pulse, whichis 90° (¹ H) pulse is produced for the X axis, so that ¹ H{¹² C} isreturned to longitudinal magnetization and water signals are removed asshown in FIG. 15B. In FIG. 16, the third proton pulse, which is 90° (¹H) pulse, is produced for the Y axis to return ¹ H{¹³ C} to longitudinalmagnetization and preserve the transverse magnetization of ¹ H{¹² C}. Inthis state, a gradient magnetic field pulse pulse is produced to therebydephase ¹ H{¹² C} and remove water signals. After that, a 90° (¹ H)pulse is produced to return ¹ H{¹³ C} to transverse magnetization andcreate the multiple-quantum coherence state.

FIG. 17 shows an HMQC pulse sequence in which gradient magnetic fieldpulse Gselection are added in order to remove single-quantum coherenceof water signals and select only multiple-quantum coherence.

In order to use the INEPT, DEPT, HSQC, or HMQC in in vivo magneticresonance spectroscopy, the localization is essential.

FIG. 18 shows a DEPT pulse sequence combined with a VSE (volumeselective excitation) pulse sequence. In the VSE sequence, a 90°selective excitation pulse and a 90° non-selective excitation pulse arecombined to put spins outside a region of interest intopseudo-saturation and make forced recovery of spins within the region ofinterest, thereby providing the localization of three axes.

However, problems associated with the combined use of the VSE sequenceand the DEPT sequence are that widely-used apparatuses cannot produceVSE pulses and the precision of localization is reduced by recovery oflongitudinal magnetization of ¹ H spins outside a region of interest.

FIG. 19 shows a DEPT sequence which was improved by Yeung et al forlocalization. In this DEPT sequence, the first 90° (¹ H) pulse for ¹ His used as a slice selective pulse, thereby achieving the localizationof one axis.

FIG. 20 shows a SZNEPT sequence which was improved by M. Saner et al inlocalization. In this sequence, two pulses for ¹ H are used as sliceselective pulses, thereby achieving the localization of two axes.

FIG. 21 shows a DEPT pulse sequence which was improved by Bomsdorf et alfor localization. In this DEPT sequence, the first 90° (¹ H) pulse andtwo 90° (¹ H) pulses resulting from division of a 180° (¹ H) pulse areused as slice selective pulses to achieve the localization of threeaxes.

In addition, the combined use of an ISIS (image selected in vivospectroscopy) technique and the DEPT sequence is also being consideredfor localization. However, this method requires two data acquisitionsteps for one-dimensional localization and eight data acquisition stepsfor three-dimensional localization. This requires a long observationtime. Further, this method also has a problem that the precision oflocalization is reduced by recovery of longitudinal magnetization.

FIG. 22 shows an HMQC sequence intended to achieve the localization ofone axis by using a 90° (¹ H) pulse for ¹ H as a slice selective pulse.

As described above, the INEPT, DEPT, HSQC, and HMQC methods havedifficulties in achieving efficient localization.

In addition, the ¹ H observation methods (HSQC, HMQC) have a problemthat water signals cannot be successfully removed.

FIG. 23 shows changes of the spectrum of the brain of a monkey with timeafter glucose in which ¹³ C is labeled with carbon is injected into itsvein. The area of this spectrum corresponds to the amount of metabolite.As shown in FIG. 24, by observing changes of the area of the spectrumwith time, information is obtained which is useful for diagnosis ofmetabolic speed by way of example. The area of the spectrum wascalculated on the basis of an approximate curve of the spectrum curve.However, the precision of the approximate curve was too low to obtainuseful information with high precision.

SUMMARY OF THE INVENTION

It is an object of the invention to provide a magnetic resonancediagnostic apparatus which permits the localization to be achievedsuccessfully by improving each of the INEPT, DEPT, HSQC, and HMQC pulsesequences.

According to an aspect of the invention there is provided a magneticresonance diagnostic apparatus which is adapted to apply to a pluralityof nuclear species radio-frequency (RF) magnetic fields corresponding totheir respective resonant frequencies, comprising: means for applying asequence of a first RF pulse, a second RF pulse, and a third RF pulse toa first nuclear species and applying a sequence of a fourth RF pulse anda fifth RF pulse to a second nuclear species to cause poralizationtransfer from spins of the first nuclear species to spins of the secondnuclear species; and means for acquiring a magnetic resonance signal ofthe second nuclear species based on the polarization transfer, andwherein the fourth RF pulse is an inversion pulse that is applied at atime that is within an interval between the first RF pulse and the thirdRF pulse and differs from the timing of the second RF pulse, and thefifth RF pulse is applied simultaneously with or after the third RFpulse.

According to other aspect of the invention, there is provided a magneticresonance diagnostic apparatus which is adapted to apply to a pluralityof nuclear species radio-frequency (RF) magnetic fields corresponding totheir respective resonant frequencies, comprising: means for applying asequence of a first RF pulse, a second RF pulse, and a third RF pulse toa first nuclear species and applying a sequence of a fourth RF pulse anda fifth RF pulse to a second nuclear species to thereby causeporalization transfer from spins of the first nuclear species to spinsof the second nuclear species; means for, after the occurrence of thepolarization transfer, applying a sixth RF pulse to the second nuclearspecies and a seventh RF pulse to the first nuclear species to therebyreturn the polarization transfer from spins of the second nuclearspecies to spins of the first nuclear species; and means for acquiring amagnetic resonance signal from the first nuclear species returned thepolarization transfer, and wherein the fourth RF pulse is an inversionpulse that is applied at a time that is within an interval between thefirst RF pulse and the third RF pulse and differs from the timing of thesecond RF pulse, the fifth RF pulse is applied simultaneously with orafter the third RF pulse, and the seventh RF pulse is appliedsimultaneously with or after the sixth RF pulse.

According to other aspect of the invention, there is provided a magneticresonance diagnostic apparatus which is adapted to apply to a pluralityof nuclear species radio-frequency (RF) magnetic fields corresponding totheir respective resonant frequencies, comprising: means for applying asequence of a first RF pulse, a second RF pulse, and a third RF pulse toa first nuclear species and applying a fourth RF pulse to a secondnuclear species; and means for acquiring a magnetic resonance signalfrom spins of the first nuclear species that are spin-spin coupled withspins of the second nuclear species, and wherein the fourth RF pulse isan inversion pulse that is applied at a time that is within an intervalbetween the first RF pulse and the third RF pulse and differs from thetiming of the second RF pulse, and the third RF pulse is applied in aphase to return spins of the first nuclear species that are notspin-spin coupled with spins of the second nuclear species to thelongitudinal magnetization.

According to other aspect of the invention, there is provided a magneticresonance diagnostic apparatus which is adapted to apply to a pluralityof nuclear species radio-frequency (RF) magnetic fields corresponding totheir respective resonant frequencies, comprising: means for applying asequence of a first RF pulse, a second RF pulse, a third RF pulse and afourth RF pulse to a first nuclear species and applying a fifth RF pulseto a second nuclear species; means for applying a dephase gradientmagnetic field pulse during an interval between the third and fourth RFpulses; and means for acquiring a magnetic resonance signal from thefirst nuclear species that are spin-spin coupled with the second nuclearspecies, and wherein the fifth RF pulse is an inversion pulse that isapplied at a time that is within an interval between the first RF pulseand the third RF pulse and differs from the timing of the second RFpulse, and the third RF pulse is applied in a phase to return spins ofthe first nuclear species that are spin-spin coupled with spins of thesecond nuclear species to the longitudinal magnetization.

According to other aspect of the invention, there is provided a magneticresonance diagnostic apparatus which is adapted to apply to a pluralityof nuclear species radio-frequency (RF) magnetic fields corresponding totheir respective resonant frequencies, comprising: means for applying asequence of a first RF pulse, a second RF pulse, and a third RF pulse toa first nuclear species and applying a fourth RF pulse and a fifth RFpulse to a second nuclear species to thereby cause polarization fromfirst nuclear spins to second nuclear spins, the fourth RF pulse is anexcitation pulse that is applied during an interval between the secondRF pulse and the third RF pulse, the fifth RF pulse is a refocus pulsethat is applied simultaneously with or after the third RF pulse; meansfor applying gradient magnetic field pulses during an interval betweenthe first and second RF pulses and during an interval between the secondand fourth RF pulses at an equal integration value with respect to time;and means for acquiring a magnetic resonance signal from the secondnuclear species with the polarization transfer.

According to other aspect of the invention, there is provided a magneticresonance diagnostic apparatus which is adapted to apply to a pluralityof nuclear species radio-frequency (RF) magnetic fields corresponding totheir respective resonant frequencies, comprising: means for applying asequence of a first RF pulse, a second RF pulse, and a third RF pulse toa first nuclear species and applying a sequence of at least a fourth RFpulse and a fifth RF pulse to a second nuclear species to thereby causepolarization transfer from first nuclear spins to second nuclear spins,the fourth RF pulse is an excitation pulse that is applied during aninterval between the second RF pulse and the third RF pulse, the fifthRF pulse is a refocus pulse that is applied simultaneously with or afterthe third RF pulse; means for applying gradient magnetic field pulsesbetween an interval the first and second RF pulses, an interval betweenthe fourth and third RF pulses and after the fifth RF pulse at an equalintegration value with respect to time; and means for acquiring amagnetic resonance signal of the second nuclear species based on thepolarization transfer.

According to other aspect of the invention, there is provided a magneticresonance diagnostic apparatus which is adapted to apply to a pluralityof nuclear species radio-frequency (RF) magnetic fields corresponding totheir respective resonant frequencies, comprising: means for applying asequence of a first RF pulse and a second RF pulse to a first nuclearspecies and applying at least a third RF pulse to a second nuclearspecies simultaneously with or after the second RF pulse to therebycause polarization transfer from first nuclear spins to second nuclearspins; means for, after the occurrence of polarization transfer,applying at least a refocus pulse as a slice selective pulse associatedwith a first axis to the first nuclear species and at least a fourth RFpulse to the second nuclear species in sequence and applying a fifth RFpulse to the first nuclear species simultaneously with or after thefourth RF pulse to thereby return polarization transfer from the secondnuclear spins to the first nuclear spins; means for acquiring a magneticresonance signal from the first nuclear species at the occurrence of thepolarization transfer; and means for applying gradient magnetic fieldpulses associated with the first axis for selecting a slice with therefocus pulse and suppressing a magnetic resonance signal from the firstnuclear species that are not spin--spin coupled with the second nuclearspins.

According to other aspect of the invention, there is provided a magneticresonance diagnostic apparatus which is adapted to apply to a pluralityof nuclear species radio-frequency (RF) magnetic fields corresponding totheir respective resonant frequencies, comprising: means for applying afirst RF pulse to a first nuclear species; means for applying a secondRF pulse to the first nuclear species after the application of the firstRF pulse to thereby produce multiple-quantum coherence between the firstnuclear species and a second nuclear species, which the first and secondnuclear species are spin--spin coupled; means for applying a refocuspulse to the first nuclear species after the application of the secondRF pulse as a slice selective pulse associated with a first axis; meansfor applying a third RF pulse to the second nuclear species after theapplication of the refocus pulse to produce single-quantum coherence ofthe first nuclear species and acquiring a magnetic resonance signal fromthe first nuclear species; and means for applying gradient magneticfield pulses for selecting a slice with the refocus pulse and forsuppressing a magnetic resonance signal from first nuclear spins thatare not spin--spin coupled with the second nuclear species.

Additional objects and advantages of the invention will be set forth inthe description which follows, and in part will be obvious from thedescription, or may be learned by practice of the invention. The objectsand advantages of the invention may be realized and obtained by means ofthe instrumentalities and combinations particularly pointed out in theappended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of the specification, illustrate presently preferred embodiments ofthe invention and, together with the general description given above andthe detailed description of the preferred embodiments given below, serveto explain the principles of the invention.

FIG. 1 shows a conventional INEPT pulse sequence;

FIG. 2 shows the state of ¹ H spins at time ta in FIG. 1;

FIG. 3 shows an example of a spectrum of ¹³ C;

FIG. 4 shows a conventional INEPT pulse sequence which has an additionaldecoupling pulse;

FIG. 5 shows a conventional INEPT pulse sequence which has additional180° pulses for ¹ H and ¹³ C;

FIG. 6 shows a conventional INEPT pulse sequence which has an additional180° pulse for ¹³ C;

FIG. 7 shows a conventional DEPT pulse sequence;

FIG. 8 shows another conventional DEPT pulse sequence;

FIG. 9 shows a conventional HSQC pulse sequence which has an additionalwater signal suppression pulse;

FIG. 10 shows an example of a two-dimensional spectrum;

FIG. 11 shows a conventional HMQC pulse sequence;

FIG. 12 shows an example of a two-dimensional spectrum;

FIG. 13 shows a conventional HSQC pulse sequence for suppressing watersignals;

FIG. 14 shows a conventional HMQC pulse sequence for suppressing watersignals;

FIGS. 15A and 15B show the states of ¹ H spins at times ta and tb inFIG. 14;

FIG. 16 shows another conventional HMQC pulse sequence for suppressingwater signals;

FIG. 17 shows a conventional HMQC pulse sequence which has additionalGselection pulses;

FIG. 18 shows a conventional DEPT pulse sequence for localization;

FIG. 19 shows another conventional DEPT pulse sequence for localization;

FIG. 20 shows still another conventional INEPT pulse sequence forlocalization;

FIG. 21 shows a further conventional DEPT pulse sequence forlocalization;

FIG. 22 shows a conventional HMQC pulse sequence for localization;

FIG. 23 shows a stack plot of metabolic change after injecting [1-¹³ C]glucose;

FIG. 24 shows changes of the area or the peak height of a spectrum;

FIG. 25 shows an arrangement of a magnetic resonance diagnosticapparatus according to a first embodiment of the invention;

FIG. 26 shows a first improved INEPT pulse sequence;

FIG. 27 shows the first improved INEPT pulse sequence which hasadditional Gadd pulses;

FIG. 28 shows a second improved INEPT pulse sequence;

FIG. 29 shows the second improved INEPT pulse sequence which has anadditional decoupling pulse;

FIG. 30 shows the second improved INEPT pulse sequence which has anadditional 180° pulse for ¹³ C;

FIGS. 31A and 31B are diagrams for use in explanation of principles oflocalization associated with the INEPT pulse sequences;

FIG. 32 shows a third improved INEPT pulse sequence corresponding to theprinciple of FIG. 31A;

FIG. 33 shows the third improved INEPT pulse sequence which hasadditional Gadd pulses;

FIGS. 34, 35 and 36 show the third pulse sequences which have anadditional decoupling pulse;

FIG. 37 shows a fourth improved INEPT pulse sequence corresponding tothe principle of FIG. 31B;

FIG. 38 shows the fourth improved INEPT pulse sequence which hasadditional Gadd pulses;

FIG. 39 shows a fifth improved INEPT pulse sequence;

FIGS. 40 and 41 are diagrams for use in explanation of the principles oflocalization associated with DEPT;

FIG. 42 shows a first improved DEPT pulse sequence corresponding to theprinciple of FIG. 40;

FIG. 43 shows a second improved DEPT pulse sequence;

FIG. 44 shows the second improved pulse sequence corresponding to theprinciple of FIG. 41;

FIG. 45 shows the second improved DEPT pulse sequence which hasadditional Gadd pulses;

FIG. 46 shows a third improved DEPT pulse sequence;

FIGS. 47A, 47B, 48A and 48B show the first and second improved pulsesequences with which the POMMIE method is used combined;

FIG. 49 shows a fourth improved DEPT pulse sequence;

FIG. 50 shows an arrangement of a magnetic resonance diagnosticapparatus according to a fourth embodiment of the invention;

FIG. 51 shows a first improved HSQC pulse sequence;

FIG. 52 shows a second improved HSQC pulse sequence;

FIG. 53 shows the basic sequence in the INEPT section;

FIGS. 54A and 54B are diagrams for use in explanation of the principlethat allows the second 180° y(¹ H) pulse for ¹ H in the INEPT section tobe used as a slice selective pulse;

FIG. 55 shows the state of ¹ H spins after a lapse of 1/(4J) from theapplication of the 180° y(¹ H) pulse;

FIG. 56 shows a third improved HSQC pulse sequence corresponding to theprinciple of FIG. 54A;

FIG. 57 shows a fourth improved HSQC pulse sequence corresponding to theprinciple of FIG. 54B;

FIG. 58 shows an improved HSQC pulse sequence in which the 180° pulse inthe reverse INEPT section is removed;

FIG. 59 shows a fifth improved HSQC pulse sequence;

FIG. 60 shows a sixth improved HSQC pulse sequence;

FIG. 61 shows a seventh improved HSQC pulse sequence;

FIG. 62 shows a coherence path;

FIG. 63 shows an eighth improved HSQC pulse sequence;

FIG. 64 shows a ninth improved HSQC pulse sequence;

FIG. 65 shows a tenth improved HSQC pulse sequence;

FIG. 66 shows an eleventh improved HSQC pulse sequence;

FIG. 67 shows an improved HSQC pulse sequence which has additional watersignal suppression pulses;

FIG. 68 shows a twelfth improved HSQC pulse sequence;

FIG. 69 shows an arrangement of a magnetic resonance diagnosticapparatus according to a fourth embodiment of the invention;

FIG. 70 shows an INEPT combined-use type pulse sequence which hasselective saturation pulses;

FIG. 71 shows an INEPT combined-use type pulse sequence in which two 90°(¹ H) pulses are used as slice selective pulses;

FIGS. 72 and 74 show INEPT combined-use type pulse sequences in whichthree 90° pulses for ¹ H are used as slice selective pulses;

FIGS. 73 and 75 show INEPT combined-use type pulse sequences in whichthe second 180° y(¹ H) pulse for ¹ H are used as a slice selectivepulse;

FIG. 76 shows an arrangement of a magnetic resonance diagnosticapparatus according to a fifth embodiment of the invention;

FIG. 77A shows a first improved HMQC pulse sequence;

FIGS. 77B and 77C show first improved HMQC pulse sequences in which GYis improved to suppress water signals;

FIG. 78 shows paths of coherence corresponding to the sequences of FIGS.77A, 77B and 77C;

FIG. 79 shows the first improved HMQC pulse sequence which hasadditional Gx and Gy pulses to suppress water signals;

FIG. 80 shows the first improved HMQC pulse sequence in which two 90°pulses for ¹³ C are shaped into a sine function;

FIG. 81 shows an HMQC pulse sequence in which selective saturationpulses are used for the localization of the third axis;

FIG. 82 shows an improved HMQC pulse sequence in which the rephasinggradient field corresponding to the slice selection gradient field isshifted to the interval between the last 90° pulse for ¹³ C and thestart of data acquisition;

FIG. 83 shows an arrangement of a magnetic resonance diagnosticapparatus according to a sixth embodiment of the invention;

FIGS. 84A through 84E show examples of multiple spectra; and

FIG. 85 shows an example of a connected spectrum.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In the invention, a first nuclear species and a second nuclear speciesthat are magnetically coupled with the first nuclear species areutilized. In this description, the first species and the second speciesare selected to be ¹ H and ¹³ C, respectively. This is, however, onlyillustrative and not restrictive. For example, the second nuclearspecies may be !15N.

Let the spin--spin coupling factor of ¹ H and ¹³ C be represented by J.Let ¹ H coupled with ¹³ C be represented by ¹ H{¹³ C} and ¹ H coupledwith ¹² C by ¹ H{¹² C}.

Further, let a radio-frequency magnetic field pulse that selectivelyexcites only ¹ H spins with respect to the a (a=X or Y) axis berepresented by a 90° a(¹ H) pulse. Let a radio-frequency magnetic fieldpulse that selectively inverts only ¹ H spins with respect to the a (a=Xor Y) axis be represented by a 180° a(¹ H) pulse. Let a radio-frequencymagnetic field pulse that selectively excites only ¹³ C spins withrespect to the a (X or Y) axis be represented by a 90° a(¹³ C) pulse.Let a radio-frequency magnetic field pulse that selectively inverts only¹³ C spins with respect to the a (X or Y) axis be represented by a 180°a(¹³ C) pulse.

First Embodiment

FIG. 25 shows an arrangement of a magnetic resonance diagnosticapparatus according to a first embodiment of the invention. A coilassembly includes a static magnetic field magnet 1, gradient coils 2, ashim coil, and a probe 4.

The static magnetic field magnet 1 provides a static magnetic fieldwithin the coil assembly. The gradient coils 2 are supplied withcurrents from a gradient coil power supply system 5 to provide gradientmagnetic field pulses along the X, Y and Z-axis directions. The shimcoil 3 is supplied with a current from a shim coil power supply tocompensate for the inhomogeneity of magnetic fields.

The probe 4 is responsive to a radio-frequency current from a ¹ Htransmitter 7 to produce a (¹ H) pulse and responsive to aradio-frequency current from a ¹³ C transmitter 8 to produce a (¹³ C)pulse.

A ¹³ C receiver 9 receives a magnetic resonance signal from ¹³ C throughthe probe 4. A data acquisition unit 11 amplifies and detects thereceived magnetic resonance signal and then converts it to a digitalsignal. A computer system 12 performs Fourier transform on the magneticresonance signal from the data acquisition unit 11 to thereby produce ¹³C spectrum data, which, in turn, is displayed on an image display unit14. A console 13 is connected to the computer system 12 to enteroperator's commands.

The first embodiment achieves the localization by using aradio-frequency magnetic field pulse for ¹ H as a slice selective pulse,not by using a radio-frequency pulse for ¹³ C. This is because thelocalization based on the ¹³ C radio-frequency magnetic field pulseresults in a positional change problem due to a chemical shift, whereasthe localization by the ¹ H radio-frequency magnetic field pulse islittle affected by such a change in position.

In the first embodiment, a radio-frequency magnetic field pulse for ¹ Hthat was produced in the prior art simultaneously with a radio-frequencymagnetic field pulse for ¹³ C is produced at a different time from thetime when that ¹³ C pulse is produced and used as a slice selectivepulse. This is because simultaneously producing a slice selective pulseand a radio-frequency field pulse for ¹³ C will degrade the flip-anglecharacteristic of the ¹³ C pulse.

First, a basic INEPT pulse sequence will be described. A 90° x(¹ H)pulse, a 180° y(¹ H) pulse and a 90° y(¹ H) pulse are sequentiallyproduced for ¹ H. A 180° (¹³ C) pulse and a 90° (¹³ C) pulse aresequentially produced for ¹³ C. The second 180° y(¹ H) pulse for ¹ H andthe first 180° (¹³ C) for ¹³ C pulse are produced simultaneously. Thethird 90° y(¹ H) pulse for ¹ H and the second 90° (¹³ C) pulse for ¹³ Care produced simultaneously.

The time interval between the first 90° x(¹ H) pulse for ¹ H and thefirst 180° (¹³ C) for ¹³ C pulse is set to 1/(4J). The time intervalbetween the first 180° (¹³ C) pulse for ¹³ C and the third 90° y(¹ H)pulse for ¹ H is also set to 1/(4J).

FIG. 26 shows a first improved INEPT pulse sequence according to thepresent embodiment. Selective saturation pulses are used as prepulsesfor the INEPT pulse sequence, which achieve the localization of oneaxis. Slice selective pulses achieve the localization of the two otheraxes.

First, spins outside a region of interest are sufficiently dephased bythe selective saturation pulses and brought into pseudo saturation. Inprinciple, saturated spins produce no signal. This will achieves thelocalization of, for example, the Z axis.

After that, the improved INEPT pulse sequence is carried out. A first90° ±x(¹ H) pulse for ¹ H is produced as a slice selective pulsesimultaneously with a gradient magnetic field pulse Gx. This willprovide the localization of the X axis.

A second 180° y(¹ H) pulse and a first 180° (¹³ C) pulse for ¹³ C areproduced simultaneously after a lapse of 1/(4J) from the time the 90°±x(¹ H) pulse is produced.

After a lapse of 1/(4J) from the first 180° (¹³ C) pulse for ¹³ C, athird 90° y(¹ H) pulse for ¹ H is produced as a slice selective pulsesimultaneously with a gradient magnetic field pulse Gy, therebyachieving the localization of the Y axis.

A second 90° (¹³ C) pulse for ¹³ C is produced after a lapse of acertain time from the time the third 90° y(¹ H) pulse for ¹ H used as aslice selective pulse associated with the Y axis is produced.

In this way, the first improved INEPT pulse sequence allows thelocalization of the three axes.

The phase of the first 90° ±x(¹ H) pulse for ¹ H is switched between +xand -x with each repetition of the pulse sequence. The polarity of asignal from ¹³ C that is based on polarization transfer is invertedaccording to that phase switching. On the other hand, the polarity of asignal from ¹³ C that is not based on polarization transfer is fixedirrespective of the switching. Thus, subtracting one of a signalobtained by the 90° +x(¹ H) pulse sequence and a signal obtained by the90° -x(¹ H) pulse sequence from the other allows only the ¹³ C signalbased on polarization transfer to be extracted.

The same effect can be obtained by, instead of switching the phase ofthe first 90° ±x(¹ H) pulse for ¹ H, switching the phase of a 90° ±y(¹H) pulse, used in place of the third 90° y(¹ H) pulse, with eachrepetition of the pulse sequence as shown in FIG. 27.

In the prior art, the localization of all the three axes is effected bythe selective saturation pulses. This will causes a problem that thelongitudinal magnetization of spins dephased by the selective saturationpulse for the localization of a first axis restores and provides asignal during a long interval from the time that selective saturationpulse is applied to the time the improved INEPT pulse sequence isstarted.

In contrast, the first improved INEPT pulse sequence is short in thatinterval and hence is less affected by such a problem than the priorart.

As shown in FIG. 27, the gradient magnetic field pulse Gadd is producedbefore and after the second 180° y(¹ H) pulse for ¹ H. In this case, theintegration value of the previous gradient magnetic field pulse Gaddwith respect to time and the integration value of the later gradientmagnetic field pulse with respect to time are set equal to each other.The gradient magnetic field pulse Gadd may be Gx, Gy, or Gz. Such agradient magnetic field pulse Gadd will compensate for the insufficiencyof the flip angle of a 180° pulse.

FIG. 28 shows a second improved INEPT pulse sequence, which implementsthe localization of the Z axis by phase encoding, not by the selectivesaturation pulse. The gradient magnetic field pulse Gz is produced priorto data acquisition. The integration value of the gradient field Gz withrespect to time is changed with each repetition of the pulse sequence.The gradient field Gz provides phase information to the magneticresonance signal as spatial information. The localization of the twoother axes is effected in the same way as the first improved INEPT pulsesequence.

As shown in FIGS. 29 and 30, a decoupling pulse may be producedcontinuously during the data acquisition time to thereby improve thesignal-to-noise ratio in the magnetic resonance signal.

FIGS. 31A and 31B show the principles of achieving the localization ofthree axes using each of the three radio-frequency magnetic field pulsesfor ¹ H as a slice selective pulse. Attention is paid herein to the factthat polarization transfer that is as efficient as the INEPT sequence iseffected when the interval between the first 180° (¹³ C) pulse for ¹³ Cand the third 90° y(¹ H) pulse for ¹ H is 1/(4J) as shown in FIG. 31A.Also, attention is paid to the fact that efficient polarization transferis effected when the interval between the first 90° (¹ H) pulse for ¹ Hand the first 180° (¹³ C) pulse for ¹³ C is 1/(4J) as shown in FIG. 31B.

This allows the second 180° y(¹ H) pulse for ¹ H to be used as a sliceselective pulse without adversely affecting the flip angle of the first180° (¹³ C) pulse for ¹³ C.

FIG. 32 shows a third improved INEPT pulse sequence corresponding to theprinciple of FIG. 31A. In this pulse sequence, a 90° ±x(¹ H) pulse, a180° y(¹ H) pulse and a 90° y(¹ H) pulse are sequentially produced for ¹H, while a 180° (¹³ C) pulse and a 90° (¹³ C) pulse are sequentiallyproduced for ¹³ C.

The interval between the first 90° ±x(¹ H) pulse and the first 180° (¹³C) pulse is set to 1/(4J). The interval τ between the first 90° ±x(¹ H)pulse and the second 180° y(¹ H) pulse is set longer than 1/(4J). Theinterval between the second 180° y(¹ H) pulse and the third 90° y(¹ H)pulse is also set to τ.

The second 180° y(¹ H) pulse and the first 180° (¹³ C) pulse are notproduced simultaneously. That is, the second 180° y(¹ H) pulse isproduced at a time different from the time when the first 180° (¹³ C)pulse is produced, specifically after the 180° (¹³ C) pulse.

The third 90° y(¹ H) pulse and the second 90° (¹³ C) pulse are notproduced simultaneously. That is, the third 90° y(¹ H) pulse is producedat a time different from the time when the second 90° (¹³ C) pulse isproduced, specifically before the 90° (¹³ C) pulse.

The three radio-frequency magnetic field pulses for ¹ H, the 90° ±x(¹ H)pulse, the 180° y(¹ H) pulse and the 90° y(¹ H) pulse, are produced asslice selective pulses associated with the three different axessimultaneously with the gradient magnetic field pulses Gx, Gy, and Gz,respectively.

The localization of the three axes is effected by using each of thethree radio-frequency magnetic field pulses for ¹ H as a slice selectivepulse associated with a different axis. Each of the three sliceselective pulses is not produced simultaneously with any one of theradio-frequency magnetic field pulses for ¹³ C, preventing the flipangles of these pulses for ¹³ C from becoming insufficient.

The interval between the 90° x(¹ H) pulse and the 180° (¹³ C) pulse maybe changed to an odd multiple of 1/(4J). Note that with CH₃, J=125 Hz,and with CH₂, J=160 Hz. That is, J varies with the coupling state. If,therefore, the interval is set relatively long, say, 3/(4J) or 5/(4J),then the difference between the optimum interval for CH₂ and the optimuminterval for CH₃ becomes large, reducing the polarization transferefficiency. For this reason, it may be said that the interval is bestset as short as possible, i.e., 1/(4J), from a viewpoint of polarizationtransfer efficiency.

However, with J=160 Hz, 1/(4J)=1.6 ms. It is very difficult for thewidely-used apparatus's power supply system to, immediately after theslice-selection gradient field GX, produce a refocusing gradientmagnetic field pulse (shown dotted in FIG. 32) corresponding to thatgradient field Gx within the interval of 1.6 ms.

As shown in FIG. 32, the rephasing gradient field is producedpolarity-inverted between the second 180° y(¹ H) pulse and the third 90°y(¹ H) pulse, not immediately after the slice-selection gradient fieldGx. This allows the widely-used apparatus to set up the pulse sequenceof FIG. 32 under the condition that 1/(4J) 1.6 ms.

The principles illustrated in FIGS. 31A and 31B are also useful for thecase where slice selection is not made. In order to remove the effect ofinsufficiency of a 180° pulse, gradient magnetic field pulses whoseintegration values with respect time are equal to each other are usuallyapplied before and after a ¹ H 180° pulse. With the conventionalsequence as shown in FIG. 1, however, it is difficult for thewidely-used apparatus to apply these gradient magnetic field pulsesbecause the interval between ¹ H RF pulses is short as describedpreviously. However, the use of the methods illustrated in FIGS. 31A and31B allows the gradient field pulses for removing the effect ofinsufficiency of a 180° pulse to be applied because the ¹ H pulseinterval can be set arbitrarily.

Further, such setting of the time of producing the rephasing gradientfield during an interval between the second and third pulses for ¹ H,not immediately after the slice-selection gradient field also providesthe following advantage. That is, since it is not required to producethe rephasing gradient field during the interval of 1.6 ms, it isallowed to produce the slice selective pulse with a width of 3 ms bymaking much use of that interval. Therefore, a long RF pulse, such asadiabatic RF pulse, can be used to improve the characterization of sliceprofile.

As shown in FIG. 33, gradient fields Gadd for compensating forinsufficiency of the 180° pulse flip angle should be added to the thirdimproved INEPT pulse sequence as well. However, care must be taken toensure that the gradient fields Gadd do not overlap in time with theradio-frequency magnetic fields in order to avoid degradation of theslice selective characteristics.

As shown in FIGS. 34, 35 and 36, the third improved INEPT pulse sequencemay be added with a decoupling pulse.

FIG. 37 shows a fourth improved INEPT pulse sequence corresponding tothe principle illustrated in FIG. 31B. The interval between the first180° (¹³ C) pulse and the third 90° y(¹ H) pulse is set to 1/(4J). Theinterval between the first 90° ±x(¹ H) pulse and the second 180° y(¹ H)pulse is set to τ longer than 1/(4J). The interval between the second180° y(¹ H) pulse and the third 90° y(¹ H) pulse is also set to τ.

The second 180° y(¹ H) pulse and the first 180° (¹³ C) pulse are notproduced simultaneously as in the third INEPT pulse sequence. That is,the second 180° y(¹ H) pulse is produced at a time different from thetime when the first 180° (¹³ C) pulse is produced, specifically afterthe 180° (¹³ C) pulse.

The third 90° y(¹ H) pulse and the second 90° (¹³ C) pulse are notproduced simultaneously. That is, the third 90° y(¹ H) pulse is producedat a time different from the time when the second 90° (¹³ C) pulse isproduced, specifically before the 90° (¹³ C) pulse.

The three radio-frequency magnetic field pulses for ¹ H, the 90° (¹ H)pulse, the 180° y(¹ H) pulse and the 90° y(H) pulse, are applied asslice selective pulses associated with the three different axessimultaneously with the gradient magnetic field pulses Gx, Gy, and Gz,respectively.

The localization of the three axes is effected by using each of thethree radio-frequency magnetic field pulses for ¹ H as a slice selectivepulse associated with a different axis. Each of the three sliceselective pulses is not applied simultaneously with any one of theradio-frequency magnetic field pulses for ¹³ C, preventing the flipangles of these pulses for ¹³ C from becoming insufficient. Further, theinterval between the 90° x(¹ H) and the second 180° x(¹ H) pulse is setlonger than 1/(4J), allowing the widely-used apparatus to produce therefocusing gradient magnetic field pulse immediately after the sliceselective gradient field Gx. In addition, the first 180° x(¹ H) pulsecan be produced in a sufficiently long width, which improves theprecision of the localization.

As with the third INEPT pulse sequence, in the fourth INEPT pulsesequence as well, gradient magnetic field pulses Gadd should be added,as shown in FIG. 38, to compensate for insufficiency of the 180° pulseflip angle. In addition, a decoupling pulse should be applied during thedata acquisition interval.

FIG. 39 shows a fifth improved INEPT pulse sequence, in which a 90° ±x(¹H) pulse, a 180° y(¹ H) pulse, a 180° y(¹ H) pulse and a 90° y(¹ H)pulse are sequentially applied for ¹ H. By applying the third 180° y(¹H) pulse after a lapse of τ' from the echo timing that occurs after adelay of τ from the second 180° y(¹ H) pulse and applying the fourth 90°y(¹ H) pulse after a lapse of τ' from the third pulse, the spin staterequired of polarization transfer can be secured at time ta immediatelybefore the fourth pulse even with the third pulse added.

The fifth improved INEPT pulse sequence uses the added third 180° y(¹ H)pulse as a slice selective pulse for the third axis.

The first 180° (¹³ C) pulse is applied during the interval between thesecond 180° y(¹ H) pulse and the echo time, the interval between theecho time and the third 180° y(¹ H) pulse, or the interval between thethird pulse and the fourth 90° y(¹ H) pulse.

Second Embodiment

The second embodiment is directed to improvements in the DEPT pulsesequence. A magnetic resonance diagnostic apparatus therefor is the samein arrangement as that shown in FIG. 25 and description thereof isomitted.

FIGS. 40 and 41 illustrate the principles of the localization in theDEPT pulse sequence. According to these principles, the polarizationtransfer is effected when the time interval between the first 90° (¹³ C)pulse for ¹³ C and the third θ ±(¹ H) pulse for ¹ H is set to 1/(4J) asshown in FIGS. 40 and 41. In addition, as shown in FIG. 41, if thesecond 180° (¹³ C) for ¹³ C is at the center of the interval from thefirst 90° (¹³ C) pulse for ¹³ C to the start of data acquisition, thenit is not required that the interval between the first 90° (¹³ C) pulseand the second 180° (¹³ C) pulse be 1/(2J). These principles allow thesecond and third radio-frequency magnetic field pulses for ¹ H to beused as slice selective pulses without making the flip angles of thefirst and second pulses for ¹³ C insufficient.

FIG. 42 shows a first improved DEPT pulse sequence corresponding to theprinciple illustrated in FIG. 40. In this pulse sequence, a 90° x(¹ H)pulse, a 180° x(¹ H) pulse and a θ° y(¹ H) pulse are sequentiallyapplied for ¹ H, while a 90° (¹³ C) pulse and a 180° (¹³ C) pulse aresequentially applied for ¹³ C.

The interval between the first 90° ±(¹³ C) pulse and the third θ° ±y(¹H) pulse is set to 1/(2J).

The interval between the first 90° x(¹ H) pulse and the second 180° x(¹H) pulse and the interval between the second 180° x(¹ H) pulse and thethird θ° y(¹ H) pulse are each set to τ longer than 1/(2J).

The second 180° x(¹ H) pulse for ¹ H and the first 90° (¹³ C) pulse forC are not applied simultaneously. That is, the second 90° x(¹ H) pulseis applied at a time different from the time when the first 90° (¹³ C)pulse is applied, specifically before that 90° (¹³ C) pulse.

The two first and second radio-frequency magnetic field pulses for ¹ H,the 90° x(¹ H) pulse and the 180° x(¹ H) pulse, are applied as sliceselective pulses associated with the two different axes simultaneouslywith the gradient magnetic field pulses Gx and Gy, respectively.

The localization of the two axes is achieved by using each of theradio-frequency magnetic field pulses for ¹ H as a slice selective pulseassociated with a different axis. Each of the two slice selective pulsesis not applied simultaneously with any one of the radio-frequencymagnetic field pulses for ¹³ C, preventing the flip angles of thesepulses for ¹³ C from becoming insufficient. The localization of threeaxes is effected by adding a selective saturation pulse for one axis tothe pulse sequence of FIG. 42.

Gradient magnetic field pulses Gadd1 or Gadd2 for compensating forinsufficiency of the flip angle of the 180° pulse are applied for the180° pulse. The field pulse Gadd1 is applied during the interval betweenthe first 90° x(¹ H) pulse and the second 180° x(¹ H) pulse and theinterval between the second 180° x(¹ H) pulse and the third θ° ±y(¹ H)pulse with an equal integration value with respect to time. The fieldpulse Gadd2 is applied during the interval between the first 90° x(¹ H)pulse and the second 180° x(¹ H) pulse, the interval between the first90° (¹³ C) pulse and the second 180° (¹³ C) pulse, and the intervalbetween the second 180° (¹³ C) pulse and the start of data acquisitionwith an equal time integration value.

In FIG. 42, the phase of the last θ ±y(¹ H) is switched between +y and-y with each repetition of the pulse sequence. The difference betweenmagnetic resonance signals for two successive pulse sequences willextract only signals from ¹³ C.

FIG. 43 shows a DEPT pulse sequence that is improved so as to achievethe localization of all the three axes by using radio-frequency magneticfield pulses for ¹ H as slice selective pulses. In this pulse sequence,a 180° ±y(¹ H) pulse is added to the interval between the 180° x(¹ H)pulse and the θ Y(¹ H) pulse. This additional pulse is applied at thecenter of the interval 2τ 'between the echo timing associated with thesecond 180° x(¹ H) pulse and the last θ Y(¹ H) pulse. The phase of theadded pulse is switched between +y and -y with each repetition of thepulse sequence.

Like the first and second radio-frequency magnetic field pulses for ¹ H,the additional pulse is used as a slice selective pulse. The first,second and third radio-frequency magnetic field pulses for ¹ H are usedas slice selective pulses for the three different axes. Thus, thelocalization of three axes is achieved.

The gradient magnetic field pulses Gadd1, Gadd2 or Gadd3 forcompensating for insufficiency of the 180° pulse flip angle are appliedfor the corresponding 180° pulse. The gradient field pulses Gadd1 areapplied during the interval between the first 90° x(¹ H) and the second180° x(¹ H) and the interval between the second 180° x(¹ H) pulse andthe echo timing to have an equal time integration value. The gradientfield pulses Gadd2 are produced in the interval between the echo timingand the added 180° x(¹ H) pulse and the first 90° (¹³ C) pulse for ¹³ Cto have an equal integration value with respect to time. The pulsesGadd3 are applied during the interval between the first 90° (¹³ C) pulseand the second 180° (¹³ C) pulse and the interval between the second180° (¹³ C) pulse and the start of data acquisition with an equalintegration value with respect to time.

FIG. 44 shows a second improved DEPT pulse sequence set up according tothe principle of FIG. 41. The second 180° (¹³ C) pulse for ¹³ C isapplied at the center of the interval between the first 180° (¹³ C)pulse and the start of data acquisition.

The interval between the first 90° (¹³ C) pulse for ¹³ C and the thirdθ° ±y(¹ H) pulse for ¹ H is set to 1/(2J). The interval between thefirst 90° (¹³ C) pulse and the second 180° (¹³ C) pulse for ¹³ C is setto 1/(2J)+τc longer than 1/(2J). The interval between the second 180°(¹³ C) pulse and the start of data acquisition is also set to 1/(2J)+τc.

Thus, the third θ° ±y(¹ H) pulse for ¹ H is not applied simultaneouslywith the second 180° (¹³ C) pulse for ¹³ C. The third pulse is appliedbefore the second pulse for ¹³ C.

Like the first and second radio-frequency magnetic field pulses for ¹ H,the third pulse for ¹ H is used as a slice selective pulse. The first,second and third radio-frequency magnetic field pulses for ¹ H are usedas slice selective pulses associated with the three different axes.Thereby, the localization of the three axes is achieved.

In order to rephase the ¹³ C spins, it is required to apply a gradientmagnetic field pulse Gz which has the same time integration value as thegradient magnetic field pulse Gz applied simultaneously with the thirdpulse for ¹ H during the interval between the second pulse for ¹³ C andthe start of data acquisition.

In the second improved DEPT pulse sequence, as shown in FIG. 45,gradient magnetic field pulses Gadd1 or Gadd2 for compensating forinsufficiency of the flip angle of a 180° pulse should be applied forthat 180° pulse. The gradient fields Gadd1 are applied during theinterval between the first and second pulses for ¹ H and the intervalbetween the second pulse for ¹ H and the first pulse for ¹³ C to have anequal integration value with respect to time. The gradient fields Gadd2are applied during the interval between the first and second pulses for¹ H, the interval between the first pulse for ¹³ C and the third pulsefor ¹ H, and the interval between the second pulse for ¹³ C and thestart of data acquisition to have an equal integration value withrespect to time.

FIG. 46 shows a third improved DEPT pulse sequence. In this pulsesequence, only the first 90° x(¹ H) pulse for ¹ H is used as a sliceselective pulse to effect the localization of one axis. The intervalbetween the first pulse and the second 180° y(¹ H) pulse is set to asshort as 1/(2J). It is difficult for the widely-used apparatus powersupply to produce a rephasing gradient magnetic field pulse (showndotted) for the slice gradient magnetic field pulse Gx during that shortinterval. This difficulty is solved by producing the rephasing gradientmagnetic field pulse in the interval between the second 180° y(¹ H)pulse and the third θ° y(¹ H).

As shown in FIGS. 47A, 47B, 48A and 48B, the POMM method published by J.M. Bulsing et al in the Journal of Magnetic Resonance, vol. 56, p. 167,(1984) may be used combined with the first and second improved DEPTpulse sequences. A 90° ±φ (¹ H) pulse is added before or after the last90° x(¹ H) pulse for ¹ H, which is used as a slice selective pulse alongwith the first and second pulses for ¹ H. The first and second pulsesand the 90° ±φ (¹ H) pulse are applied as slice selective pulsesassociated with the three different axes. Thereby, the localization ofthe three axes is achieved. The phase of the 90° ±φ (¹ H) pulse isinverted with respect to the φ axis with each repetition of the pulsesequence. The difference between magnetic resonance signalscorresponding to two successive pulse sequences will eliminate unwantedsignals resulting from the addition of the 90° ±φ (¹ H) pulse.

The above-described improved DEPT sequence may be modified as shown inFIG. 49.

Third Embodiment

The third embodiment relates to improvements in the HSQC (HeteronuclearSingle Quantum Coherence) method which is one of the ¹ H observationmethods for observing signals from ¹ H. For ¹ H observation, the axiallocalization and the removal of water signals are important. The thirdembodiment and a fifth embodiment to be described later are intended toachieve the localization of axes and remove water signals.

FIG. 50 shows an arrangement of a magnetic resonance diagnosticapparatus according to the third embodiment. In this figure, likereference numerals are used to denote corresponding parts to those inFIG. 25 and description thereof is omitted. A ¹ H receiver 16 is addedto the arrangement of FIG. 25 in order to receive signals from ¹ H spinsthrough the probe 4.

The basic HSQC sequence comprises a preceding INEPT section, anintermediate single-quantum coherence section, and a succeedingreverse-INEPT section.

In the INEPT section, a 90° x(¹ H) pulse, a 180° y(¹ H) pulse and a 90°y(¹ H) pulse are sequentially applied for ¹ H, while a 180° (¹³ C) pulseand a 90° (¹³ C) pulse are sequentially applied for ¹³ C. The intervalbetween the first 90° x(¹ H) pulse for ¹ H and the first 180° (¹³ C)pulse for ¹³ C is set to 1/(4J). The interval between the first 180° (¹³C) pulse and the and the third 90° y(¹ H) pulse for ¹ H are also set to1/(4J).

In the reverse-INEPT section, a 90° (¹ H) pulse and a 180° (¹ H) pulseare sequentially applied for ¹ H, while a 90° (¹³ C) pulse and a 180°(¹³ C) pulse are sequentially applied for ¹³ C. The interval between the90° (¹³ C) pulse for ¹³ C and the 180° (¹ H) pulse for ¹ H is set to1/(4J). The 180 (¹ H) pulse for ¹ H is produced at the center of theinterval between the 90° (¹ H) pulse and the start of data acquisition.

In the single-quantum coherence section, a 180° (¹ H) pulse is appliedduring an interval between the INEPT pulse sequence and thereverse-INEPT pulse sequence.

FIG. 51 shows a first improved HSQC pulse sequence. Prior to the HSQCsequence, the localization of two axes (Gy and Gz) is achieved byselective saturation pulses. The first 90° x(¹ H) pulse for ¹ H is usedas a slice selective pulse for localizing the remaining axis (Gx). Thus,the localization of three axes is achieved.

Water signals are removed by a water signal suppression pulse before theimproved HSQC sequence is carried out. The water suppression pulse,which is a radio-frequency magnetic field pulse, selectively excitesonly water spins. The gradient magnetic field pulses Gx, Gy and Gz alongthe three axes sufficiently dephase only excited water spins, therebysubstantially suppressing the generation of signals from water spins.

FIG. 52 shows a second improved HSQC pulse sequence. The localization ofone axis (Gz) is achieved by selective saturation pulses before the HSQCsequence is carried out. A first 90° x(¹ H) pulse for ¹ H in the INEPTsection is used as a slice selective pulse for localizing another axis(Gx). A 180° (¹ H) pulse in the single-quantum coherence period t1 isused as a slice selective pulse for localizing the remaining axis (Gy).Thus, the three axes are localized.

A pulse train in the gradient magnetic field pulse Gy, which is appliedwith the 180° (¹ H) pulse (slice selective pulse) during thesingle-quantum coherence period t1, is adjusted so as to satisfyequation (1) or (2) below so that it can have a function of localizingthe Y axis and a function of suppressing water signals. G1, G2, G3 andG4 are defined as follows:

G1: The integration value with respect to time of the gradient field Gyapplied during the interval T1 between the center of the last 90° x(¹³C) pulse for ¹³ C in the INEPT section and the center of 180° (¹ H)pulse in the single-quantum coherence period t1.

G2: The integration value with respect to time of the gradient field Gyproduced during the interval T2 between the center of the 180° (¹ H)pulse in the single-quantum coherence section and the center of thefirst 90° x(¹³ C) for ¹³ C in the reverse-INEPT section.

G3: The integration value with respect to time of the gradient field Gyproduced during the interval T3 between the center of the first 90° x(¹H) pulse for ¹³ C in the reverse-INEPT section and the center of thesecond 180° (¹ H) for ¹³ C in the reverse-INEPT section.

G4: The integration value with respect to time of the gradient field Gyproduced during the interval T4 between the center of the 180° (¹ H)pulse for ¹³ C in the reverse-INEPT section and the start of dataacquisition.

    γ2·G1+γ2·G2+γ1·G3-γ1.multidot.G4=0                                                 (1)

    γ2·G1+γ2·G2-γ1·G3+γ1.multidot.G4=0                                                 (2)

where γ1 is the gyromagnetic ratio of the first nuclear species and γ2is the gyromagnetic ratio of the second nuclear species.

When the first nuclear species is ¹ H and the second nuclear species is¹³ C, γ1=4 and γ2=1. Then, equations (1) and (2) are respectivelyrewritten as follows:

    G1+G2+4G3-4·G4=0                                  (3)

    G1+G2-4G3+4·G4=0                                  (4)

In the case of ¹ H and ¹³ C, therefore, by applying the gradientmagnetic field pulse train, including slice-selection gradient fields,in such a way as to satisfy equation (3) or (4) only the single-quantumcoherence path for ¹³ C can be selected to suppress mainly watersignals.

As with the improved INEPT sequence, in the improved HSQC sequence aswell, the localization of three axes can be achieved by using threeradio-frequency magnetic field pulses for ¹ H as slice selective pulsesassociated with different axes without using the selective saturationpulses. In the second HSQC sequence, the first 90° x(¹ H) pulse in theINEPT section and the 180° (¹ H) pulse in the single-quantum coherencesection are used as slice selective pulses. By using, in addition tothese two pulses, the second 180° (¹ H) pulse in the INEPT section as aslice selective pulse, the localization of three axes can be effected.

FIG. 53 shows the basic sequence for INEPT. FIGS. 54A and 54B illustratethe principles of permitting the second 180° y(¹ H) pulse for ¹ H in theINEPT section to be used as a slice selective pulse. FIG. 55 shows thestate of ¹ H spins. If this state is obtained at the center of the third90° -y(¹ H) pulse for ¹ H in the INEPT section, the polarizationtransfer is achieved. The principle is the same as that described inconnection with FIGS. 31A and 31B.

The above-described method can be applied to the reverse-INEPT section.That is, six ¹ H pulses are used in the HSQC sequence of the invention.Any one of these pulses may be used as a selective excitation pulse.Several embodiments therefor will be described below. Although, in someof these embodiments, a decoupling pulse is applied, it need notnecessarily be applied.

FIG. 56 shows a third improved HSQC pulse sequence that corresponds tothe principle illustrated in FIG. 54A. In the third HSQC pulse sequence,a first 90° x(¹ H) for ¹ H and a second 180° y(¹ H) pulse for ¹ H in theINEPT section and a 180° (¹ H) pulse in the single-quantum coherenceperiod t1 are used as slice selective pulses for different axes, therebyachieving the localization of three axes.

FIG. 57 shows a fourth improved HSQC pulse sequence corresponding to theprinciple illustrated in FIG. 54B. In the fourth improved HSQC pulsesequence as well, by using a first 90° x(¹ H) for ¹ H and a second 180°y(¹ H) pulse for ¹ H in the INEPT section and a 180° (¹ H) pulse in thesingle-quantum coherence section as slice selective pulses for differentaxes, the localization of three axes is achieved.

In the HSQC sequence as well, gradient magnetic field pulses Gadd shouldbe applied to compensate for insufficient flip angles of the 180°pulses.

As shown in FIGS. 58 and 59, the 180° pulses in the reverse-INEPTsection are applied to rephase spins dispersed by chemical shifts andmagnetic field inhomogeneity. Thus, it cannot be said that the 180°pulses in the reverse-INEPT section are essential. If the 180° pulsesare removed from the reverse-INEPT section, then equations (5) and (6)are adopted for the gradient magnetic field pulse train for suppressingwater signals. Here, equations (5) and (6) are general expressions, andequations (7) and (8) are adopted for ¹ H and ¹³ C combination. In thiscase, the definition of G3 is changed as follows:

G3: The integration value with respect to time of the gradient magneticfield pulse Gy applied during the interval T3 between the center of thefirst 90° x(¹ H) pulse for ¹ H in the reverse-INEPT section and thestart of data acquisition.

    γ2·G1+γ2·G2+γ1·G3=0 (5)

    γ2·G1+γ2·G2-γ1·G3=0 (6)

    G1+G2+4G3=0                                                (7)

    G1+G2-4G3=0                                                (8)

Even when the 180° pulses are removed from the reverse-INEPT section,the interval between the last 90° y(¹ H) pulse for ¹ H in thereverse-INEPT section and the start of data acquisition (the beginningof the decoupling pulse) remains unchanged from 1/(2J). Note thatalthough the embodiment which has both a function of localization of theY axis and a function of removing water signals is described inconnection with the HSQC sequence only, it goes without saying that itis useful to any sequence in which a 180° pulse for ¹ H is appliedwithin the single-quantum coherence period of ¹³ C (within the t1period).

FIG. 59 shows a fifth improved HSQC pulse sequence. In this pulsesequence, the localization of three axes is achieved by using a first90° x(¹ H) pulse for ¹ H and a third 90° -y(¹ H) pulse for ¹ H in theINEPT section and a 180° (¹ H) pulse in the single-quantum coherencesection as slice selective pulses for different axes.

FIG. 60 shows a sixth improved HSQC pulse sequence, which is intended toachieve the localization of three axes by using three excitationradio-frequency magnetic field pulses each of which provides a 90° flipfor ¹ H spins. That is, the localization of three axes is achieved byusing a first 90° x(¹ H) for ¹ H and a third 90° -y(¹ H) pulse for ¹ Hin the INEPT section and a second 90° y(¹ H) pulse in the reverse-INEPTas slice selective pulses associated with different axes.

A 90° pulse is superior to a 180° pulse in slice selectivecharacteristics. Thus, the sixth improved HSQC sequence is superior inthe characterization of slice profile to the HSQC sequence that uses a180° pulse for the localization of one axis.

FIG. 61 shows a seventh improved HSQC pulse sequence, which, byselecting all of coherence paths, solves a problem that the signalstrength becomes 1/2. To this end, a first gradient field G1 is producedduring the interval between a second 90° x(¹³ C) for ¹³ C in the INEPTsection and a 180° (¹ H) pulse in the single-quantum coherence period t1and a second gradient field G1 is produced during the interval betweenthe 180° (¹ H) pulse in the single-quantum coherence period and a first90° x(¹³ C) pulse for Q13C in the reverse-INEPT section. The first andsecond gradient magnetic field pulses are opposite to each other inpolarity and adjusted so that their integration value with respect totime becomes equal. Such adjustment allows all the coherence paths to beselected.

FIG. 62 shows all the coherence paths. I and S correspond to ¹ H and ¹³C, respectively. First, the coherence path separates into S⁺ and S⁻immediately after polarization transfer (T3). In this state, the firstand second gradient magnetic field pulses G1 and G2 are applied. As aresult, refocusing is performed in both S⁺ and S⁻, i.e., in all thecoherence paths. In contrast, ¹ H spins that, like water, are notcombined with ¹³ C spins are dephased. As a result, all the coherencepaths for ¹ H and ¹³ C spins are selected, while no coherence path forwater is selected.

FIG. 63 shows an eighth improved HSQC pulse sequence. In this sequence,a first 90° x(¹ H) pulse for ¹ H in the reverse-INEPT section puts the ¹H spins in water in longitudinal magnetization and the ¹ H{¹³ C} spinsin transverse magnetization. The ¹ H spins and the ¹ H{¹³ C} spins inwater are developed into transverse magnetization and longitudinalmagnetization, respectively, through a 180° y(¹ H) and a 90° y(¹ H)pulse. A gradient magnetic field pulse Gspoil is applied after the 90°y(¹ H) pulse, dephasing the ¹ H spins in water. However, the ¹ H{¹³ C}spins are not dephased because they are in the longitudinalmagnetization. Thus, water signals are suppressed.

FIG. 64 shows a ninth improved HSQC pulse sequence, which is combinedwith the method by A. G. Palmer (see the Journal of Magnetic Resonancevol. 93, pp. 151 to 170, 1991) in order to improve sensitivity. Afterthe reverse-INEPT section a pulse sequence in block B is carried out. Inthis block, a 90° (¹ H) pulse, a 180° (¹ H) pulse and a 90° (¹ H) pulseare sequentially applied for ¹ H. A 90° (¹³ C) pulse and a 180° (¹³ C)pulse are sequentially applied for ¹³ C. The 90° (¹ H) pulse and the 90°(¹³ C) pulse are applied simultaneously. The 180° (¹ H) pulse and the180° (¹³ C) pulse are applied simultaneously. Such a pulse sequenceallows the signal strength to be increased in principle by a factor of√2.

FIG. 65 shows a tenth improved HSQC pulse sequence. In this pulsesequence, the localization of three axes is effected by using the first90° x(¹ H) pulse and the second 180° (¹ H) pulse for ¹ H in the INEPTsection and the 180° (¹ H) pulse in the reverse-INEPT section as sliceselective pulses associated with different axes.

FIG. 66 shows an eleventh improved HSQC pulse sequence. In this pulsesequence, a 180° (¹ H) pulse in the single-quantum coherence section anda first 90° x(¹ H) pulse for ¹ H and a second 180° (¹ H) pulse for ¹ Hin the reverse-INEPT section are used as slice selective pulses fordifferent axes, thereby achieving the localization of three axes.

In the eleventh improved HSQC pulse sequence, a slice-selection gradientmagnetic field pulse Gx applied with the 180° (¹ H) pulse (sliceselective pulse) during the period t1 is adjusted to satisfy thefollowing condition. Suppose that an integration value with respect totime of the gradient magnetic field pulse Gx produced during theinterval T1 between the center of the 90° x(¹³ C) in the INEPT sectionand the center of the 180 (¹ H) pulse in the single-quantum coherencesection is G1 and an integration value with respect to time of thegradient magnetic field pulse Gx produced during the interval T2 betweenthe center of the 180° (¹ H) and the center of the first 90° (¹³ C)pulse in the reverse-INEPT section is G2. Then, the gradient magneticfield pulse Gx is adjusted, including the slice-selection gradientmagnetic field pulse, so as to satisfy the condition that G1:G2=1:-1.

Water signals may be suppressed by generating water suppression pulsesas prepulses as shown in FIG. 67. That is, the ¹ H spins in water arefirst selectively excited by a 90° pulse and then sufficiently dephasedby gradient magnetic field pulses Gx, Gy and Gz.

FIG. 68 shows a twelfth improved HSQC pulse sequence. In this sequence,data is acquired before and after a 180° (¹ H) pulse in thesingle-quantum coherence period t1. Data acquired during the period t1and data acquired during an interval t2 after the reverse-INEPT sequenceare subjected to proper signal processing such as arithmetic mean, whichimproves the signal-to-noise ratio. Two-dimensional data σ(ω¹ H, ω¹³ C)acquired during the interval t2 is projected onto the ω¹³ C axis andconverted to one-dimensional data σ1(ω¹³ C). The data σ1(ω¹³ C) and thedata σ2(ω¹³ C) in the period t1 are added and averaged. The number ofdata sampling points over the period t1 changes each time phase encodingchanges and does not generally coincide with the number of times phaseencoding is performed. For this reason, σ1(ω¹³ C) and σ2(ω¹³ C) cannotbe simply added. Thus, it is required to adjust the number of samplingpoints by processing such as zero-filling.

Fourth Embodiment

The fourth embodiment of the invention is directed to combined use of ageneral data acquisition pulse sequence such as a spin echo method andan INEPT pulse sequence and improvements in localization by theINEPT-combined pulse sequence for acquiring magnetic resonance signalsfrom ¹ H spins (¹ H observation method).

FIG. 69 shows an arrangement of a magnetic resonance diagnosticapparatus according to the fourth embodiment. In this figure, likereference numerals are used to denote corresponding parts to those inthe arrangement of FIG. 50 and description thereof is omitted.

The methods of localization described in connection with the improvedINEPT pulse sequences can be applied to such an INEPT-combined pulsesequence. In a pulse sequence shown in FIG. 70, spins outside a regionof interest are sufficiently dephased by selective saturation pulses toprovide the localization of three axes. In a pulse sequence of FIG. 71,two 90° (H) pulses in the INEPT section in block A are used as sliceselective pulses to provide the localization of two axes. In a pulsesequence of FIG. 72, a 90° (¹ H) pulse is added to the INEPT section ofblock B. Three 90° pulses for ¹ H, including the added pulse, are usedas slice selective pulses to provide the localization of three axes. Inthese pulse sequences as well, of course, gradient magnetic field pulsesGadd should be generated to compensate for insufficiency of 180°-pulseflip angles. In addition, a decoupling pulse should also be appliedduring data acquisition interval. Moreover, as shown in a pulse sequenceof FIG. 75, a second 180° y(¹ H) pulse for ¹ H may be applied as a sliceselective pulse at a time different from the time a first 180° (¹³ C)pulse is applied.

Since the pulse sequences of the fourth embodiment are adapted toobserve ¹ H spins, it is necessary to suppress water signals (¹ H{¹²C}). FIGS. 73 and 74 illustrate methods of suppressing the watersignals.

FIG. 73 illustrate a preferable method of suppressing water signals. Athird 90° (¹ H) pulse for ¹ H is applied in the phase of the X axis. Thestate of ¹ H spins immediately before that third pulse is as shown inFIG. 2. That is, the magnetization of ¹ H{¹³ C} is polarized along the Xaxis (i.e., transverse magnetization). On the other hand, ¹ H{¹² C}becomes transversely magnetized along the Y axis. In such a spin state,when the third 90° (¹ H) pulse is applied in the phase of the X axis,the magnetization of ¹ H{¹³ C} is polarized along the X axis as it was,that is, the transverse magnetization is maintained. On the other hand,¹ H{l² C} is brought to longitudinal magnetization. Consequently, watersignals can be suppressed.

FIG. 74 illustrates another method of suppressing water signals. Betweenthe second 180° y(¹ H) pulse and the last 90° (¹ H) pulse for ¹ H a 90°y(¹ H) pulse for ¹ H is added. The state of ¹ H spins immediately beforethat added pulse is as shown in FIG. 2. That is, the magnetization of ¹H{¹³ C} is polarized along the X axis into transverse magnetization. Onthe other hand, ¹ H{¹² C} becomes transversely magnetized along the Yaxis. In such a spin state, when the additional pulse is applied, ¹ H{¹³C} becomes longitudinally magnetized and the magnetization of ¹ H{¹² C}remains unchanged from transverse magnetization. In this state, when adephase gradient magnetic field pulse Gx is applied, the magnetizationof ¹ H{¹² C} is sufficiently dephased. On the other hand, themagnetization of ¹ H{¹³ C} is not affected by the gradient field pulseGx. Consequently, water signals can be suppressed.

As shown in the pulse sequence of FIG. 75, a 180° y(¹ H) pulse may beadded for use as a slice selective pulse.

Fifth Embodiment

The fifth embodiment relates to improvements in an HMQC (HeteronuclearMultiple Quantum Coherence) method which is one of the ¹ H observationmethods. For the ¹ H observation methods, important subjects are thelocalization of axes and the removal of water signals. The fifthembodiment is intended for the localization of axes and the suppressionof water signals.

FIG. 76 shows an arrangement of a magnetic resonance diagnosticapparatus according to the fifth embodiment. In this figure, likereference numerals are used to denote corresponding parts to those inthe arrangement of FIG. 50 and description thereof is omitted.

FIG. 77A shows a first improved HMQC pulse sequence. In this pulsesequence, a 90° (¹ H) pulse and a 180° (¹ H) pulse are sequentiallyapplied for ¹ H. Two 90° (¹³ C) pulses are sequentially applied for ¹³C.

The interval between the center of the first 90° (¹ H) pulse for ¹ H andthe center of the first 90° (¹³ C) pulse for ¹³ C is set to 1/(2J). Thisinterval may be set to an odd multiple of 1/(2J). General nuclearspecies to be observed include CH₂ and CH₃. With 3/(2J) or 5/(2J), thedifference between the optimum interval for CH₂ and the optimum intervalfor CH₃ becomes large, resulting in reduced polarization transferefficiency. For this reason, it is preferable that the interval be setto 1/(2J).

The interval between the center of the first 90° (¹³ C) pulse and thecenter of the second 90° (¹³ C) pulse for ¹³ C is set to themultiple-quantum coherence period t1. The second 180° (¹ H) pulse isapplied at the center of the multiple-quantum coherence period t1.

The first 90° (¹ H) pulse and the second 180° (¹ H) pulse are used asslice selective pulses associated with different axes, effecting thelocalization of two axes. The localization of the remaining axis iseffected herein by phase encoding of Gz. This phase encoding provides atwo-dimensional spectrum of C--H correlation.

A slice-selective gradient magnetic field pulse Gx is applied with thefirst 90° (¹ H) pulse used as a slice selective pulse. A rephasegradient field pulse for the gradient field pulse Gx is usually appliedimmediately after that pulse Gx as shown dotted. Here, the rephasegradient field pulse is applied during the interval between the second90° (¹³ C) pulse and the start of data acquisition after themultiple-quantum coherence period t1. However, since the intervalbetween the center of the first 90° (¹ H) pulse for ¹ H and the centerof first 90° (¹³ C) pulse for ¹³ C is as short as 1/(2J), it isdifficult for the widely-used apparatus to apply a slice refocusgradient field during this interval. However, the present embodimentallows even the widely-used apparatus to apply the rephase gradientfield pulse. This means that even the widely-used apparatus can use thefirst 90° (¹ H) pulse for ¹ H as a slice selective pulse.

When the second 180° (¹ H) pulse within the multiple-quantum coherenceperiod t1 is used as a slice selective pulse, a slice-selection gradientfield pulse Gy for that pulse takes part in the multiple-quantumcoherence. Therefore, some consideration will be needed to apply thatgradient field pulse. Four intervals are defined as follows:

T1: The interval between the center of the first 90° (¹ H) pulse for ¹ Hand the center of the first 90° (¹³ C) pulse for ¹³ C (immediatelybefore the multiple-quantum coherence period).

T2: The interval between the center of the first 90° (¹³ C) pulse (thebeginning of the multiple-quantum coherence period) and the center ofthe second 180 (¹ H) pulse for ¹ H.

T3: The interval between the center of the second 180° (¹ H) pulse for ¹H and the center of the second 90° (¹³ C) pulse for ¹³ C (the end of themultiple-quantum coherence period).

T4: The interval between the center of the second 90° (¹³ C) pulse for¹³ C (the end of the multiple-quantum coherence period) and the start ofdata acquisition.

The integration values with respect to time of the gradient field pulsesGy generated during the intervals T1, T2, T3 and T4 are defined as G1,G2, G3, and G4, respectively. The gradient magnetic field pulse Gy is agradient magnetic field pulse associated with the same axis as aslice-selection gradient magnetic field pulse corresponding to the 180°(¹ H) pulse used as a slice selective pulse. The integration value withrespect to time is given by ∫Gy(t)dt where Gy(t) represents changes ofmagnetic field strength with time.

To realize the multiple-quantum coherence, the ratio in area among G1,G2, G3 and G4 is set in accordance with the method described by JesusRuiz-Cabello et al in the Journal of Magnetic Resonance, vol. 100, p.282, 1992.

FIG. 78 shows coherence paths corresponding to the pulse sequence ofFIG. 78. I corresponds to ¹ H and S corresponds to ¹³ C. Let position ber and the gyromagnetic ratios of ¹ H and ¹³ C be γ^(H) and γ^(C),respectively. The phases φI and φS corresponding to the integrationvalues G of I and S gradient magnetic field pulses with respect to timeare given by

    φI=γ∥·G·r             (9)

    φS=γC·G·r                      (10)

The multiple-quantum coherence that follows paths of (I+S+→I-S+) and(I-S-→I+S-) is realized by setting the ratio among G1, G2, G3 and G4 soas to satisfy the equation

    γ1·G1+(γ1+γ2)·G2+(-γ1+γ2).multidot.G3-γ1·G4=0                          (11)

Also, the multiple-quantum coherence that follows paths of (I+S-→I-S-)and (I-S+→I+S+) is realized by setting the ratio among G1, G2, G3 and G4so as to satisfy the equation

    γ1·G1+(γ1-γ2)·G2+(-γ1+γ2).multidot.G3-γ1·G4=0                          (12)

By adjusting a pulse train for gradient field Gy including a sliceselection gradient field pulse so that either of equations (11) and (12)is satisfied, the multiple-quantum coherence corresponding to either ofequations (11) and (12) will be realized.

In the examples of FIGS. 77A and 77B, the pulse train for gradient fieldGy is set in accordance with equation (11) in the following ratio:

G1:G2:G3:G4=0:2:2:1

In the examples of FIG. 77C, on the other hand, the pulse train forgradient field Gy is set in accordance with equation (12) in thefollowing ratio:

G1:G2:G3:G4=0:3:5:0

If the pulse train for gradient field Gy including a slice-selectiongradient field pulse is adjusted in this manner so as to satisfyequation (11) or (12), then the 180° pulse for ¹ H produced within themultiple-quantum coherence period can be used as a slice selective pulseto effect the localization and removal of water signals.

As shown in FIG. 79, in addition to setting the pulse train for gradientfield Gy so as to satisfy equation (11) or (12), it is possible to usethe gradient fields Gx and Gy along the axes different from that for theslice-selection gradient field Gy for selection of multiple-quantumcoherence.

As shown in FIG. 80, by shaping two 90° pulses for ¹³ C into a sinefunction to thereby narrow their frequency bandwidth, the number ofsteps in a two-dimensional spectrum can be reduced.

As shown in FIG. 81, selective saturation pulses may be used to localizethe third axis instead of using phase encoding. Likewise, an ISIS pulsemay be used for that purpose.

As shown in FIG. 82, a rephase gradient field for a slice-selectiongradient field may be produced during the interval between the last 90°pulse for ¹³ C and the start of data acquisition.

Sixth Embodiment

The sixth embodiment relates to an improvement in curve fittingprocessing of MR spectra.

FIG. 83 shows an arrangement of a magnetic resonance diagnosticapparatus according to the sixth embodiment. In this figure, likereference numerals are used to denote corresponding parts to those inthe arrangement of FIG. 50 and description thereof is omitted. Asequence controller 19 controls the gradient coil power supply system 5,transmitters 7 and 8, receivers 9 and 16, and data acquisition unit 12to carry out a pulse sequence for an MR spectrum. A magnetic resonancesignal thus generated is sampled according to a predetermined samplingfrequency. A collection of data obtained by a sequence of samplingoperations is defined a data set. One spectrum is obtained from one dataset. The pulse sequence is repeated at a predetermined repetition timeTR. The collection of data set is also repeated at the same repetitiontime. The computer system 18 subjects each of data sets to Fouriertransform individually to obtain a plurality of spectra that havedifferent corresponding times. The corresponding time to a spectrum isdefined as the time of acquiring a data set used to obtain thatspectrum. The computer system 18 performs curve fitting on the spectra.The curve fitting will be described below.

FIGS. 84A through 84E show exemplary spectra that differ incorresponding time. As shown in FIG. 85, the spectra are connected in asequential order of corresponding time. The curve fitting is performedon the connected spectra.

A model equation σ(ω, ti) of a spectrum is given by equation (13) below.Re represents the real part and Im represents the imaginary part. Aprocess that makes the model equation approximate to the connectedspectra is referred to curve fitting.

    ρ(ω,ti)=([Re+iIm]exp(iφ)

    Re=A/T2,/[(ω-ωo)2+(1/T2*)2]

    Im=A(ω-ωo)/[(ω-ωo)2+(1/T2*)2]      (13)

Equation (13) contains four unknown parameters, i.e., the spectrum areaA, the reciprocal T2. of half-value width, the chemical shift ωo, andthe phase φ. The important thing is that the three parameters, T2., ωo,φ, are the same for a plurality of spectra, and the parameter thatdiffers among spectra, i.e., the parameter that is considered to be afunction of time, is only the spectrum area A indicating the amount ofmetabolite.

That is, the total number of parameters used in the curve fittingprocess for the connected spectra is not 4×n but 3+n with n being thenumber of spectra to be connected.

For this reason, the present embodiment in which curve fitting isperformed on connected spectra is greater in fitting precision than theprior art in which curve fitting is performed on each spectrum. This isbecause, in the present embodiment, although the number of processingpoints is increased by a factor of n, the number of parameters to besought is 3+n in contrast to 4×n in the prior art.

It is preferable from a viewpoint of processing precision that spectrabe connected for subsequent curve fitting except such a spectrum asshown in FIG. 84A in which a peak level is lower than a thresholdcorresponding to noise level. Instead of connecting spectra, A(t) may besought by seeking T2*, ωo and φ from each spectrum, averaging each ofthem, fixing each of them to the corresponding resultant average value,and performing curve fitting under the conditions that the number ofparameters at each time is one.

Further, there is also provided a method of imposing limitations onA(t). By replacing A in the above model equation with a time function off(t), limitations can be imposed on A(t) to improve processingprecision.

The above description is directed to a one-component system. In the caseof a multi-component system as well, a model equation can be created ina similar manner to perform curve fitting. In this case as well, theparameters are Ai(t), ωoi, T2*i, and φi (i indicate spectrum numbers)and hence it is only Ai that becomes a function of time. The phase φi,which is represented by φi=a(ω-ωo)+b (a, b are constants), may be addedto the model equation.

Additional advantages and modifications will readily occur to thoseskilled in the art. Therefore, the invention in its broader aspects isnot limited to the specific details, and representative devices shownand described herein. Accordingly, various modifications may be madewithout departing from the spirit or scope of the general inventiveconcept as defined by the appended claims and their equivalents.

What is claimed is:
 1. A magnetic resonance diagnostic apparatus whichis adapted to apply to a plurality of nuclear species radio-frequency(RF) magnetic fields corresponding to their respective resonantfrequencies, comprising:means for applying a sequence of a first RFpulse, a second RF pulse, and a third RF pulse to a first nuclearspecies and applying a fourth RF pulse to a second nuclear species; andmeans for acquiring a magnetic resonance signal from spins of said firstnuclear species that are spin--spin coupled with spins of said secondnuclear species, and wherein said fourth RF pulse is an inversion pulsethat is applied at a time that is within an interval between said firstRF pulse and said third RF pulse and differs from the timing of saidsecond RF pulse, and said third RF pulse is applied in a phase to returnspins of said first nuclear species that are not spin--spin coupled withspins of said second nuclear species to the longitudinal magnetization.2. The apparatus according to claim 1, wherein at least one of saidfirst, second and third RF pulses is a slice selective pulse that isapplied with a slice selection gradient magnetic field pulse.
 3. Theapparatus according to claim 1, wherein said second RF pulse is arefocus pulse.
 4. The apparatus according to claim 1, wherein saidfourth RF pulse is applied after a lapse of a time corresponding to anodd multiple of 1/(4J) from the application of said first RF pulse whereJ is the spin--spin coupling constant of said first and second nuclearspins.
 5. The apparatus according to claim 1, wherein said fourth RFpulse is applied a time corresponding to an odd multiple of 1/(4J)before the application of said third RF pulse where J is the spin--spincoupling constant of said first and second nuclear spins.
 6. Theapparatus according to claim 1, wherein said fifth RF pulse is applied atime corresponding to an odd multiple of 1/(4J) before the applicationof said third RF pulse where J is the spin--spin coupling constant ofsaid first and second nuclear spins.
 7. A magnetic resonance diagnosticapparatus which is adapted to apply to a plurality of nuclear speciesradio-frequency (RF) magnetic fields corresponding to their respectiveresonant frequencies, comprising:means for applying a sequence of afirst RF pulse, a second RF pulse, a third RF pulse and a fourth RFpulse to a first nuclear species and applying a fifth RF pulse to asecond nuclear species; means for applying a dephase gradient magneticfield pulse during an interval between said third and fourth RF pulses;and means for acquiring a magnetic resonance signal from said firstnuclear species that are spin--spin coupled with said second nuclearspecies, and wherein said fifth RF pulse is an inversion pulse that isapplied at a time that is within an interval between said first RF pulseand said third RF pulse and differs from the timing of said second RFpulse, and said third RF pulse is applied in a phase to return spins ofsaid first nuclear species that are spin--spin coupled with spins ofsaid second nuclear species to the longitudinal magnetization.
 8. Theapparatus according to claim 7, wherein at least one of said first,second, third and fourth RF pulses is a slice selective pulse that isapplied with a slice gradient magnetic field pulse.
 9. The apparatusaccording to claim 7, wherein said second RF pulse is a refocus pulse.10. The apparatus according to claim 7, wherein said fifth RF pulse isapplied after a lapse of a time corresponding to an odd multiple of1/(4J) from the application of said first RF pulse where J is thespin--spin coupling constant of said first and second nuclear spins.